Effects of Early Clozapine Treatment on Remission Rates in Acute
                    Schizophrenia (The EARLY Trial): Protocol of a Randomized-Controlled
                    Multicentric Trial

Elias Wagner; Wolfgang Strube; Thomas Görlitz; Aslihan Aksar; Ingrid Bauer; Mattia Campana; Joanna Moussiopoulou; Alexander Hapfelmeier; Petra Wagner; Silvia Egert-Schwender; Robert Bittner; Kathrin Eckstein; Igor Nenadić; Tilo Kircher; Berthold Langguth; Eva Meisenzahl; Martin Lambert; Sigrid Neff; Berend Malchow; Peter Falkai; Dusan Hirjak; Kent-Tjorben Böttcher; Andreas Meyer-Lindenberg; Christiane Blankenstein; Stefan Leucht; Alkomiet Hasan

doi:10.1055/a-2110-4259

Pharmacopsychiatry, Table of Contents

CC BY-NC-ND 4.0 · Pharmacopsychiatry 2023; 56(05): 169-181
DOI: 10.1055/a-2110-4259

Original Paper

Effects of Early Clozapine Treatment on Remission Rates in Acute Schizophrenia (The EARLY Trial): Protocol of a Randomized-Controlled Multicentric Trial

EARLY Study Group*

Elias Wagner

¹Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany

,

Wolfgang Strube

²Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany

,

Thomas Görlitz

²Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany

,

Aslihan Aksar

²Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany

,

Ingrid Bauer

²Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany

,

Mattia Campana

¹Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany

,

Joanna Moussiopoulou

¹Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany

,

Alexander Hapfelmeier

³Institute of AI and Informatics in Medicine, School of Medicine, Technical University of Munich, Munich, Germany

⁴Institute of General Practice and Health Services Research, School of Medicine, Technical University of Munich, Munich, Germany

,

Petra Wagner

⁵Münchner Studienzentrum, Technical University of Munich, School of Medicine, Munich, Germany

,

Silvia Egert-Schwender

⁵Münchner Studienzentrum, Technical University of Munich, School of Medicine, Munich, Germany

,

Robert Bittner

⁶Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany

,

Kathrin Eckstein

⁷Clinic for Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany

,

Igor Nenadić

⁸Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany

,

Tilo Kircher

⁸Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany

,

Berthold Langguth

⁹Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany

,

Eva Meisenzahl

¹⁰Department of Psychiatry and Psychotherapy, LVR-Klinikum Düsseldorf, Kliniken der Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

,

Martin Lambert

¹¹Department of Psychiatry and Psychotherapy, Centre for Psychosocial Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany

,

Sigrid Neff

¹²Department of Psychiatry and Psychotherapy 1 und 2, Rheinhessen-Fachklinik Alzey, Academic Hospital of the University of Mainz, Alzey, Germany

,

Berend Malchow

¹³Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany

,

Peter Falkai

¹Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany

,

Dusan Hirjak

¹⁴Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

,

Kent-Tjorben Böttcher

¹⁴Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

,

Andreas Meyer-Lindenberg

¹⁴Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

,

Christiane Blankenstein

⁵Münchner Studienzentrum, Technical University of Munich, School of Medicine, Munich, Germany

,

Stefan Leucht

¹⁵Department of Psychiatry and Psychotherapy, Technical University of Munich, School of Medicine, Munich, Germany

,

Alkomiet Hasan

²Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany

› Author Affiliations

Abstract

Background Quick symptomatic remission after the onset of psychotic symptoms is critical in schizophrenia treatment, determining the subsequent disease course and recovery. In this context, only every second patient with acute schizophrenia achieves symptomatic remission within three months of initiating antipsychotic treatment. The potential indication extension of clozapine—the most effective antipsychotic—to be introduced at an earlier stage (before treatment-resistance) is supported by several lines of evidence, but respective clinical trials are lacking.

Methods Two hundred-twenty patients with acute non-treatment-resistant schizophrenia will be randomized in this double-blind, 8-week parallel-group multicentric trial to either clozapine or olanzapine. The primary endpoint is the number of patients in symptomatic remission at the end of week 8 according to international consensus criteria (‘Andreasen criteria’). Secondary endpoints and other assessments comprise a comprehensive safety assessment (i. e., myocarditis screening), changes in psychopathology, global functioning, cognition, affective symptoms and quality of life, and patients’ and relatives’ views on treatment.

Discussion This multicentre trial aims to examine whether clozapine is more effective than a highly effective second-generation antipsychotics (SGAs), olanzapine, in acute schizophrenia patients who do not meet the criteria for treatment-naïve or treatment-resistant schizophrenia. Increasing the likelihood to achieve symptomatic remission in acute schizophrenia can improve the overall outcome, reduce disease-associated burden and potentially prevent mid- and long-term disease chronicity.

Key Words

schizophrenia - randomized-controlled trial - clozapine - remission - second-line treatment

Full Text

References

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